Cancer antigens and methods
There are disclosed inter alia polypeptides and nucleic acids encoding said polypeptides which are useful in the treatment, prevention and diagnosis of cancer, particularly non small cell lung cancer, especially lung squamous cell carcinoma and melanoma, especially cutaneous melanoma.
1 . A composition comprising an isolated polypeptide and an immunostimulant, wherein:
(a) the isolated polypeptide consists of an amino acid sequence comprising at least 9 contiguous residues of SEQ ID NO: 1 or 2;
(b) the isolated polypeptide comprises an amino acid sequence having at least 90% identity over the entire length of SEQ ID NO: 1 or 2;
(c) the isolated polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4; or
(d) the amino acid sequence of the isolated polypeptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4.
2 . The composition of claim 1 , wherein the immunostimulant is selected from the group consisting of aluminum salts, saponins, immunostimulatory oligonucleotides, oil-in-water emulsions, aminoalkyl glucosaminide 4-phosphates, lipopolysaccharides and derivatives thereof, TLR4 ligands, TLR7 ligands, TLR8 ligands, TLR9 ligands, IL-12, and interferons.
3 . A fusion protein comprising a first polypeptide and one or more additional polypeptides, wherein the first polypeptide:
(a) consists of an amino acid sequence comprising at least 9 contiguous residues of SEQ ID NO: 1 or 2;
(b) comprises an amino acid sequence having at least 90% identity over the entire length of SEQ ID NO: 1 or 2;
(c) comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4; or
(d) consists of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-4.
4 . An isolated antigen-binding polypeptide which is immunospecific for a polypeptide as set forth in claim 1 , optionally wherein the antigen-binding polypeptide is an antibody or a T cell receptor, or an antigen-binding fragment of any one thereof.
5 . A vector or artificial nucleic acid sequence encoding a polypeptide, wherein the polypeptide:
(a) consists of an amino acid sequence comprising at least 9 contiguous residues of SEQ ID NO: 1 or 2;
(b) comprises an amino acid sequence having at least 90% identity over the entire length of SEQ ID NO: 1 or 2;
(c) comprises the amino acid sequence of SEQ ID NO: 1 or 2; or
(d) consists of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-4.
6 . The artificial nucleic acid sequence of claim 5 , wherein the artificial nucleic acid is mRNA.
7 . A method of preparing a T-cell population comprising stimulating and amplifying T-cells ex vivo using a polypeptide as set forth in claim 1 .
8 . A T-cell population obtained by the method of claim 7 .
9 . A method of preparing an antigen presenting cell population, comprising introducing into antigen presenting cell ex vivo a polypeptide as set forth in claim 1 , or a nucleic acid sequence encoding the polypeptide.
10 . An antigen presenting cell population obtained by the method of claim 9 .
11 . An exosome comprising a polypeptide or a nucleic acid sequence encoding the polypeptide, wherein the polypeptide:
(a) comprises an amino acid sequence comprising at least 9 contiguous residues of SEQ ID NO: 1 or 2;
(b) comprises an amino acid sequence having at least 90% identity over the entire length of SEQ ID NO: 1 or 2;
(c) comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4; or
(d) consists of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-4.
12 . A method of stimulating an immune response in a subject, the method comprising administering to the subject a therapeutically effective amount of a polypeptide as set forth in claim 1 , or a nucleic acid sequence encoding the polypeptide.
13 . A method of stimulating an immune response in a subject, the method comprising administering to the subject a therapeutically effective amount of the T-cell population of claim 8 .
14 . A method of stimulating an immune response in a subject, the method comprising administering to the subject a therapeutically effective amount of the antigen presenting cell population of claim 10 .
15 . A method of treating a subject suffering from a cancer expressing a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or 2, or an immunogenic fragment or variant thereof, the method comprising administering to the subject a therapeutically effective amount of a polypeptide as set forth in claim 1 , or a nucleic acid sequence encoding the polypeptide.
16 . A method of treating a subject suffering from a cancer expressing a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or 2, or an immunogenic fragment or variant thereof, the method comprising administering to the subject a therapeutically effective amount of the T-cell population of claim 8 .
17 . A method of treating a subject suffering from a cancer expressing a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or 2, or an immunogenic fragment or variant thereof, the method comprising administering to the subject a therapeutically effective amount of the antigen presenting cell population of claim 10 .
18 . A method of diagnosing a subject as suffering from a cancer, the method comprising determining if cells of the subject comprise a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or 2, or an immunogenic fragment or variant thereof, or a nucleic acid sequence expressing the polypeptide, wherein the presence of the polypeptide or nucleic acid sequence in the cells indicates that the subject has cancer.
19 . A method of making the composition of claim 1 , the method comprising combining an immunostimulant with an isolated polypeptide, wherein:
(a) the isolated polypeptide consists of an amino acid sequence comprising at least 9 contiguous residues of SEQ ID NO: 1 or 2;
(b) the isolated polypeptide comprises an amino acid sequence having at least 90% identity over the entire length of SEQ ID NO: 1 or 2;
(c) the isolated polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4; or
(d) the amino acid sequence of the isolated polypeptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4.
20 . An isolated peptide:
(i) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1 and 2;
(ii) consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4; or
a salt thereof, and/or a composition thereof.